ENCePP Guide on Methodological Standards in Pharmacoepidemiology

10.2.2. Vaccine effectiveness

10.2.2.1. Definitions

Vaccine effects
and impact of vaccination programmes in post-licensure studies (Vaccine 2013;31(48):5634-42) reviews and delineates, among the various
evaluations of vaccine intervention, what applies to the effectiveness of
vaccine and to the impact of vaccination programmes, proposes epidemiological
measures of public health impact, describes relevant methods to measure these
effects and discusses the assumptions and potential biases involved.

10.2.2.2. Traditional cohort and
case-control studies

Generic protocols for retrospective case-control studies and retrospective cohort studies to assess the
effectiveness of rotavirus vaccination in EU Member States based on computerised
databases were published by the European Centre for Disease Prevention and
Control (ECDC). They describe the information that should be
collected by country and region in vaccine effectiveness studies and the data
sources that may be available to identify virus-related outcomes a vaccine is
intended to avert, including hospital registers, computerised primary care
databases, specific surveillance systems (i.e. laboratory surveillance, hospital
surveillance, primary care surveillance) and laboratory registers. Based on a
meta-analysis comprising 49 cohort studies and 10 case-control studies, Efficacy and effectiveness of influenza vaccines in elderly
people: a systematic review (Lancet 2005;366(9492):1165-74)
highlights the heterogeneity of outcomes and study populations included in such
studies and the high likelihood of selection bias.

10.2.2.3. Screening method

The screening method estimates
vaccine effectiveness by comparing vaccination coverage in positive cases of a
disease (e.g. influenza) with the vaccination coverage in the population from
which the cases are derived (e.g., the same age group). If representative data
on cases and vaccination coverage are available, it can provide an inexpensive
and ready-to-use method that can be useful in providing early effectiveness
estimates or identify changes in effectiveness over time. However, Application of the screening method to monitor influenza vaccine
effectiveness among the elderly in Germany (BMC Infect Dis. 2015;15(1):137) emphasises that accurate and age-specific
vaccine coverage rates are crucial to provide valid VE estimates. Since
adjusting for important confounders and the assessment of product-specific VE is
generally not possible, this method should be considered only a supplementary
tool for assessing crude VE.

10.2.2.6. Test negative
design

The article The test-negative design for estimating influenza vaccine
effectiveness (Vaccine 2013;31(17):2165-8) explains the rationale,
assumptions and analysis of the test-negative study as applied to influenza VE.
Study subjects are all persons who seek care for an acute respiratory illness
and influenza VE is estimated from the ratio of the odds of vaccination among
subjects testing positive for influenza to the odds of vaccination among subject
testing negative. This design is less susceptible to bias due to
misclassification of infection and the confounding by health care-seeking
behaviour, at the cost of difficult-to-test assumptions.

Effectiveness
of rotavirus vaccines in preventing cases and hospitalizations due to rotavirus
gastroenteritis in Navarre, Spain (Vaccine 2012;30(3):539-43)
evaluates effectiveness using a test negative case-control design based on
electronic clinical reports. Cases were children with confirmed rotavirus and
controls were those who tested negative for rotavirus in all samples. The
test-negative design was based on an assumption that the rate of gastroenteritis
caused by pathogens other than rotavirus is the same in both vaccinated and
unvaccinated persons. This approach may rule out differences in parental
attitude when seeking medical care and of physician differences in making
decisions about stool sampling or hospitalisation. A limitation is sensitivity
of antigen detection which may underestimate vaccine effectiveness. In addition,
if virus serotype is not available, it is not possible to study the association
between vaccine failure and a possible mismatch of vaccine strains and
circulating strains of virus.

10.2.2.7. Case coverage
design

10.2.2.8. Impact assessment

A generic study protocol to
assess the impact of rotavirus vaccination in EU Member States
has been published by the ECDC. It recommends the information that needs to be
collected to compare the incidence/proportion of rotavirus cases in the period
before and after the introduction of the vaccine. These generic protocols need
to be adapted to each country/regions and specific situation.

The impact of vaccination can be
quantified in children in the age group targeted for the vaccine (overall
effect) or in children of other age groups (indirect effect). The direct effect
of a vaccine, however, needs to be defined by the protection it confers given a
specific amount of exposure to infection and not just a comparable exposure. Direct
and indirect effects in vaccine efficacy and effectiveness (Am J
Epidemiol 1991; 133(4):323-31) describes how parameters intended to measure
direct effects must be robust and interpretable in the midst of complex indirect
effects of vaccine intervention programmes.

First year
experience of rotavirus immunisation programme in Finland (Vaccine
2012; 31(1):176-82) estimates the impact of a rotavirus immunisation programme
on the total hospital inpatient and outpatient treated acute gastroenteritis
burden and on severe rotavirus disease burden during the first year after
introduction. The study may be considered as a vaccine-probe-study, where
unspecific disease burden prevented by immunisation is assumed to be caused by
the agent the vaccine is targeted against.

10.2.2.9. Methods to study
waning immunity

The study of vaccine
effectiveness against diseases where immunity wanes over time requires
consideration of both the within-host dynamics of the pathogen and immune system
as well as the associated population-level transmission dynamics. Implications of vaccination and waning immunity (Proc
Biol Sci 2009; 276(1664):2071-80) seeks to combine immunological and
epidemiological models for measles infection to examine the interplay between
disease incidence, waning immunity and boosting.